Diethyl carboxamide

Heterocycles were explored as replacements for the nonphenolic ring (Table 3) [19]. Unsubstituted thiazoles, pyridines, and thiophenes gave active agonists, but with little or no selectivity. While an TV-methyl imidazole had little if any opioid agonist activity in this series, often additional substituents on the heterocycles provided potent compounds with delta opioid receptor selectivity. For instance, compound 34, a thiophene with a diethyl carboxamide, displayed selective delta opioid receptor agonism (although no binding selectivity was observed). 

The stalwart diethyl carboxamide, while a powerful DMG, suffers from treacherous hydrolytic stability, a consequence which has recently been overcome by the development of the N-cumyl carboxamide (Scheme 4) [11]. Thus, the readily available 1 undergoes smooth metalation and acceptance of a variety of electrophiles if DMF is used, the intermediate hy-droxyphthalimidine 2 may be further metalated and subjected to electrophile quench to af-... 

Di(or Bis)[N(2, 2 2 -trinitroethyl)-carboxamide]-piperazine. See under Diethyl-carboxamide-piperazine in this Vol. 

A[,A/-diethyl-l,3,4,6,7,ll -hexaliydro-2-hydroxy-9,10-dimethoxy-2Ff-ben2o-(i7)-quinoli2ine-3-carboxamide acetate hydrochloride) (16) may be made by the method described in Reference 14. 

Chemical Name N,N-Diethyl-4-methyl-1-plperazine-carboxamide citrate Common Name —... 

Benz[l,2-e][l,3]oxazin[3,4-a]azepin-6-one (15) is cleaved rapidly in cold ethereal ethylamine to /V.A-diethyl-2-(2-hydroxyphcnyl)-l//-azepinc-1-carboxamide (90% mp 121 -122°C), whereas acidic hydrolysis yields the intramolecularly hydrogen bonded 2-(2-hydro-xyphenyl)-3//-azepine (16).156... 

Et2NH (25 mL. large excess) was cautiously added to a cooled stirred suspension of crude 5-oxo-4-phenyl-4,5-dihydro-l//-l,2,4-benzotriazcpine-3-carbonyl chloride (10, R1 = Ph, R2 = H 5.0 g, 17 mmol) in benzene (100 mL) below 25 C and stirring was continued for 2h. H20 was added to dissolve the F,t2NH HOI formed and the insoluble yellow residue, A%V-diethyl-5-oxo-4-phenyl-4,5-dihydro-l//-l,2,4-benzodiazepine-3-carboxamide (llg) was collected, washed with H20 and recrystallizcd (95% EtOH) yield 4.0 g (70%) mp 202-204 C. 

CN 2-(acetyloxy)-N -diethyl-1,3,4,6,7,11 b-hexahydro-9,10-dimcthoxy-2//-benzo[a]quinolizine-3-carboxamide... 

Chloro-l,2,3-thiadiazole-4-carboxamides 38 react with the sodium salt of diethyl malonate to give the corresponding malonic acid derivatives 39. The yield in these reactions falls as the electron-releasing properties of the 4-substituents in the aromatic ring increase (Equation 8) <1997JCM396>. 

Generally, the reactions of amines and 2-acylmalonates afforded not only the corresponding 1-(substituted amino)alkylidenemalonates (301), but also carboxamides and diethyl malonate (39JA2890 54JIC711 77GEP2705446). 

In addition to the parent heterocycle, both AT,N-diethyl-l-methylpyr-role-3-carboxamide and l-methylpyrrole-3-carboxaldehyde have been selectively a-lithiated in the 2-position (85TL6213 87JOC104), the latter compound via the intermediacy of an a-(Af-methylpiperazino) alkoxide (Scheme 6). The a-amino alkoxide is formed in situ, via the addition of... 

The Reformatsky reactions of ethyl a-bromopropionate and related esters with N-substituted 6-bromo-2-oxochromene-3-carboxamides in a mixed diethyl ether-benzene-HMPA-THF solvent system give substituted 9-bromo-2,3,4,4a,5,10b-hexahydro-l//-chromeno[3,4-f]pyridine-2,4,5-triones (HMPA = hexamethylphosphoramide Scheme 45) <2004RJ0892>. Without the THF present in the mixed-solvent system, the reaction stops at the intermediate Wbenzyl-6-bromo-4-(l-alkoxycarbonylalkyl)-2-oxochroman-3-carboxamide stage. 

NORLYSERGIC ACID, 6-ALLYL-N,N-DIETHYLAMIDE 6-NORLYSERGAMIDE, 6-ALLYL-N,N-DIETHYL N,N-DIETHYLNORLYSERGAMIDE, 6-ALLYL N-(6)-ALLYLNORLYSERGIC ACID, N,N-DIETHYLAMIDE 9,10-DIDEHYDRO-6-ALLYL-N,N-DIETHYLERGOLINE-8b-CARBOXAMIDE... 

ACID LYSERGIDE D-LYSERGIC ACID DIETHYLAMIDE METH-LAD D-LYSERGAMIDE, N,N-DIETHYL N,N-DIETHYL-D-LYSERGAMIDE 9,10-DIDEHYDRO-N,N-DIETHYL-6-METHYLERGOLINE-8b-CARBOXAMIDE... 

Coumalyl chloride (330) reacts normally with ethyleneimine to give the carboxamide (333), but primary and other secondary amines such as benzylamine, r-butylamine, diethyl-amine and pyrrolidine give unsaturated anhydrides (332), possibly through an acyclic intermediate (331). Aniline gives a mixture of both kinds of product (78JOC4415). 

The action of gaseous ammonia on diethyl chromone-2,6-dicarboxylate (478) is a good example of the different reactivity between identical substituents in the same molecule. The 2-carboxylate function is more reactive even than an ester group in a side chain such as —0CH2C02Et, which is unaffected by ammonia. This is consistent with the low electron density of C-2.2-Carboxamides, such as (479), need drastic conditions for their dehydration... 

Benzo[6]thiophene-2-carboxamides have been prepared by treatment of 2-benzo[6]thienyllithium with isocyanates,564 but are more conveniently obtained from the appropriate acid chloride by the conventional procedure.334,481,548,556,564,686-688 The acid chlorides react with diazomethane to give the diazoketone,218,689 and with dimethylcadmium 76,90 or diethyl ethoxymagnesium malonate218,336... 

The amino moiety of the 3-carbohydrazide group of unsaturated and 6,7,8,9-tetrahydro-4-oxo-47/-pyrido[l,2-n]pyrimidine-3-carbohydrazides was condensed with acetone and 5-nitro-2-furoaldehyde (830MR687 88EUP252809). The reaction of 6-methyl-6,7,8,9-tetrahydro-4-oxo-4//-pyrido[l,2-a]pyrimidine-3-carbohydrazide with diethyl 2-[2-dimethyl-amino)vinyl]-6-methylpyridine-3,5-dicarboxylate in boiling ethanol for 4 hours afforded N-( 1,6-naphthyridin-6-yl)-4-oxo-4//-pyrido[ 1,2-a]pyrimi-dine-3-carboxamide 426 (85MIP1). 

A comparison of diethyl amide 107, 3-pentyl ketone 108, 3-pentyl ether 109, and alcohol 110 was conducted in order to examine the effects of the side-chain conformation on both potency and selectivity in the carboxamide series of inhibitors (Fig. 14).100 The ketone, ether, and alcohol resembled the amide in that all showed selective inhibitory activity towards influenza A NA. An sp2-hybridized center was found to contribute to the potency of 107 and 108. 

N1 RN - ERGOlINE-G-bata-CARBOXAMIDE, 9,10-DI0EHT0RO-N,N-DIETHYL-6-METHYL- - 50-37-3... 

A solution of 0.634 g (2.0 mmol) of 2-(benzyloxycarbonyl)-decahydro-(4aS,8aS)-isoquinoline-3(S)-carboxylic acid in 6 ml of dimethoxyethane was treated with 0.23 g (2.0 mmol) of N-hydroxysuccinimide and 0.412 g (2.0 mmol) of dicyclohexylcarbodiimide. The mixture was stirred at room temperature for 18 hours. The mixture was filtered and the filtrate was evaporated to give 0.879 g of the N-hydroxysuccinimide ester of the foregoing acid in the form of a pale yellow oil. A solution of 0.828 g (2.0 mmol) of the foregoing N-hydroxysuccinimide ester in 5 ml of dichloromethane was stirred, cooled to 0°C and treated with 0.219 g (3.0 mmol) of tert.butylamine. The mixture was stirred at 0°C for 2 h and then at room temperature for 4.5 h. The mixture was then washed with 2 M hydrochloric acid, sodium carbonate solution and sodium chloride solution, dried over anhydrous magnesium sulphate and evaporated. The residue was dissolved in 20 ml of diethyl ether and filtered. The filtrate was evaporated to give 0.712 g of 2-(benzyloxycarbonyl)-N-tert-butyl-decahydro-(4aS,8aS)-isoquinoline-3(S)-carboxamide in the form of a white solid. 

A solution of 561 mg of 2-[3(S)-amino-2(R)-hydroxy-4-phenylbutyl]-N-tert-butyl-decahydro-(4aS,8aS) -isoquinoline-3(S)-carboxamide and 372 mg of N-(benzyloxycarbonyl)-L-asparagine in 20 ml of dry tetrahydrofuran was cooled in an ice/salt mixture. 189 mg of hydroxybenzotriazole, 161 mg of N-ethylmorpholine and 317 mg of dicyclohexylcarbodiimide were added and the mixture was stirred for 16 h. The mixture was then diluted with ethyl acetate and filtered. The filtrate was washed with aqueous sodium bicarbonate solution and sodium chloride solution. The solvent was removed by evaporation and the residue was chromatographed on silica gel using dichloromethane/methanol (9 1) for the elution to give 434 mg of 2-[3(S)-[[N-(benzyloxycarbonyl)-L-asparaginyl]amino]-2(R)-hydroxy-4-phenyl butyl]-N-tert-butyl-decahydro-(4aS,8aS)-isoquinoline-3(S)-carboxamide as a white solid from methanol/diethyl ether. 

Dichloro-/V,/V-diethyl-1,8-naphthyridine-3-carboxamide (35) with N,N diethylisobutyrohydrazide gave 5-chloro-fV,fV-diethyl-9-isopropyl[ 1,2,4]tria-zolo 4,3- 1,8 Inaphthyridine-1 -carboxamide (36) (Dowtherm A, 155°C ... 

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